Aprea AB has announced that the European Medicines Agency (EMA) has granted its drug candidate APR-246 orphan drug designation for the treatment of ovarian cancer. Aprea is currently conducting a Phase Ib/II trial of APR-246 in combination with standard of care chemotherapy in patients with relapsed platinum sensitive high-grade serous ovarian cancer.
APR-246 is an innovative, first-in-class, anti-cancer agent with the potential to restore p53 activity in patients where p53 is non-functional or mutated. “To the company’s knowledge, APR-246 is the only compound in clinical development that can restore normal function of the p53 protein and thereby induce efficient cancer cell death. The orphan drug designation offers significant benefits during the forthcoming development and commercialization of this potentially ground-breaking treatment,” said Bruno Lucidi, CEO of Aprea and Karolinska Development.
APR-246 has previously been tested in a first-in-human dose finding study. Based on the results of the Phase I study as a single agent in a total of 32 patients, the safety and pharmacokinetic profile of APR-246 allows for combination with standard of care chemotherapy. Furthermore, preclinical ex vivo studies with human ovarian cancer cells treated with APR-246 in combination with chemotherapy showed clear synergistic effects of the two treatments combined.
Owing to the widespread occurrence of mutations in p53, the therapeutic approach of APR-246 may be applied in many types of cancers. The potential impact in ovarian cancer alone is substantial - currently, around 600,000 women are living with ovarian cancer worldwide. Approximately 60% of the ovarian cancer patients have an advanced stage disease at diagnosis, and among these patients, the 5-year survival rate is lower than 30%. Aprea’s ongoing Phase Ib/II study includes ovarian cancer patients that have relapsed from first-line chemotherapy where the median overall survival is 17 months.
Cancers develop and spread due to the malfunction of the cells’ normal growth control mechanisms. The cancer suppressing gene p53 is mutated in approximately 50% of all cancers, whereby cells lack functional p53 protein and the most important suicide mechanism is impaired. This allows for cancer cell survival and rapid tumor growth. Aprea has developed substances that can restore normal function to the p53 protein and thereby induce efficient cancer cell death and overcome resistance to antitumoral therapy.
Obtaining orphan drug designation for APR-246 in the European Union is an important regulatory milestone and also provides incentives to support development, including fee reductions and a ten year period of market exclusivity after product approval.